Ferric iron containing compounds are useful in the treatment of a number of disorders, including, but not limited to, hyperphosphatemia and metabolic acidosis. Previous studies and inventions have reported the use of ferric compounds in binding with dietary phosphates, thereby affording the control over phosphate retention in patients suffering from renal failure and associated hyperphosphatemia (U.S. Pat. No. 5,753,706; U.S. Pat. No. 6,903,235; CN 1315174, U.S. Pat. No. 8,093,423). Elevated amounts of phosphate in the blood can be removed by administering ferric iron containing compounds such as ferric citrate. U.S. Pat. No. 5,753,706 discloses compositions consisting of ferric citrate, ferric acetate, and combinations thereof, in a unit dosage of about 500 mg to about 1,000 mg.
WO 2011/011541 discloses ferric citrate tablets comprising 65 wt % to 92 wt % of ferric citrate and 4.5 wt % to 30 wt % binder, wherein at least 80% of the ferric citrate in the tablet is dissolved in a time less than or equal to 60 minutes.
WO 2012/005340 discloses ferric citrate tablets comprising polyvinyl alcohol-polyethylene glycol graft copolymer and polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer. The tablets comprise 70 wt % ferric citrate.
WO 2003/092658 discloses a process for preparing compressed tablets having good mechanical strength. The pharmaceutically active ingredient(s) and excipient(s) are granulated in the presence of a granulating liquid comprising 5-30% microcrystalline cellulose by a kneading or a fluidization spraying process.
WO 2008/149894 discloses a process for producing tablet or capsule comprising a granule, wherein the granule further includes coated core particle. The core is composed of at least 50 wt % microcrystalline cellulose, in which the active pharmaceutical ingredient is sprayed onto the core.
U.S. Pat. No. 6,149,943 discloses a method for preparing a pharmaceutically active particle, which includes about 40 wt % to 75 wt % microcrystalline cellulose as inert core coated with about 25 wt % to 60 wt % pharmaceutically active ingredient. The coating of the microcrystalline cellulose is performed in the absence of a granulation step using a spray coating technique. Further disclosed is a method wherein the coated particles and excipients are compressed to form tablets.
One of the challenges of formulating ferric citrate in solid dosage forms is its relatively high dosage. Thus, in order to prepare dosage forms having properties (e.g., size) compatible with the end user, ferric citrate compositions typically contain high percentages of the active ingredient relative to excipients. Production of such dosage forms containing ferric citrate in high content is associated with problems such as moldability during tableting, cracking, and difficulty in maintaining suitable hardness, while not affecting disintegration and dissolution properties of the dosage forms.
A need in the art exists for ferric citrate compositions that incorporate therapeutically effective doses of the active ingredient to effectively prevent and/or treat hyperphosphatemia and metabolic acidosis, that overcome the aforementioned disadvantages.